The optimal clinical management of an acute ischemic insult to the brain remains problematic. To test the effectiveness and clinical applicability of various therapies, we have designed a baboon model which closely parallels the most common manifestation of human cerebrovascular disease. We can reversibly occlude the middle cerebral artery of unanesthetized baboons with a unique vascular occluder designed by the principle investigator. With this model we are able to investigate various therapeutic regimens to determine their place in the management of stroke. We are investigating barbiturate coma in temporary and permanent MCA (middle cerebral artery) occlusions. To date we have demonstrated that six hour MCA occlusion results in greater morbidity and mortality than permanent MCA occlusion. Furthermore, barbiturate coma for 96 hours in permanent MCA occlusion baboons results in a worse outcome than permanent MCA occlusion primates without treatment. The most striking protection of 96 hour barbiturate coma occurs in 6 hour MCA occlusion animals in whom therapy is started thirty minutes following signs of ischemia. Barbiturate coma started four hours following 6 hour MCA occlusion resulted in greater morbidity and mortality than no treatment. We are now investigating further therapeutic maneuvers to extend the grace period between onset of cerebral ischemia and irreversible brain damage.